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Professor Giovanna R. Mallucci FMedSci

Professor Giovanna R. Mallucci, FMedSci

Associate Director of the UK Dementia Research Institute at the University of Cambridge

Van Geest Professor of Clinical Neurosciences

Honorary Consultant neurologist at CUH/CPFT

E-mail:gm522[at]cam.ac.uk

Website: https://ukdri.ac.uk/centres/cambridge

UK Dementia Research Institute, University of Cambridge
Island Research Building
Cambridge Biomedical Campus
University of Cambridge

Cambridge CB2 0AH

Research Interests

My lab is interested in understanding mechanisms of neurodegeneration. The central theme is the identification of common pathways across the spectrum of these disorders (which include Alzheimer's and related diseases) that are relevant for both mechanistic insights and therapy. We focus both on ‘toxic’ processes that can be targeted to prevent neuronal death, and on regenerative processes that can be harnessed for repair. Using mouse models, we described the pathogenic role of the unfolded protein response (UPR) in neurodegeneration, which led to the discovery of the first small molecule - an inhibitor of this pathway - to prevent neurodegeneration in vivo. We have now identified repurposed drugs that are able to prevent neurodegeneration in mouse models of disease and are poised for clinical trials in humans. We also recently discovered the phenomenon of failure of synaptic repair processes in neurodegeneration and the underlying mechanisms: failure of another stress response involving 'cold shock' proteins, which we have successfully harnessed for neuroprotection. We aim to translate this research for new treatments for dementia.

Key Publications

Please see my google scholar profile for a full publication list.

  • Halliday M, Radford H, Zents KAM, Verity NC, Smith E, Ortori CA, Barrett DA, Bushell M and  Mallucci GR. Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice. Brain 2017, 140(6):1768-1783.
  • Radford H, Moreno JA, Verity N, Halliday M and MallucciGR. PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia.  Acta Neuropathologica. 2015 Nov;130(5):633-42.
  • Halliday M, Radford H, Sekine Y, Moreno JA, Verity N, le Quesne J, Ortori CA, Barrett DA, Fromont C, Fischer PM, Harding HP, Ron Dand Mallucci GR. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death & Disease 2015 6:e1672.
  • Peretti D, Bastide A, Verity N, Guerra Martin M, Molloy C, Moreno JA, Radford H, Steinert J, Dinsdale D, Willis AE and Mallucci GR. RBM3 mediates structural plasticity and the protective effects of cooling in neurodegenerative disease. Nature 2015 518(7538):236-9.
  • Moreno JA, Halliday M, Molloy C, Axten JM, Willis AE, Ortori CA, Barrett DA, Fischer PM and Mallucci GR.  Oral treatment targeting the unfolded protein response prevents prion neurodegeneration and clinical disease in mice. Science Translational Medicine, 2013, 5,206ra138.
  • Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Guerra Martin M, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, M Bushell and Mallucci GR. Sustained translational repression by eIF2α−P mediates prion neurodegeneration. Nature 2012, 485, 507-11